Food, specific dietary components, and the fluid volume with which a drug is administered have all been shown to influence the rate and extent of absorption of orally administered drugs. Studies previously carried-out in this laboratory have shown that the absorption of tetracycline, aspirin, ampicillin, amoxicillin, and erythromycin products may be severely inhibited by food while the absorption of tetracycline, aspirin, amoxicillin and erythromycin is also inhibited when these compounds are administered with small (20-25 ml) accompanying water volumes to fasted individuals. In the proposed studies, which are an extension of our previous work, we shall examine drug-food and drug-fluid volume interactions from practical, pharmacokinetic and mechanistic viewpoints. Attention will focus on interaction affecting the thiazide diruetics chlorothiazide and hydrochlorothiazide. These agents need to be filtrated to a patient's condition and yet have poor bioavailability charcteristics. The influence of food and fluid volume will also be examined on the availability of the oral cephalosporins cephradine, cephalexin, and cefaclor. These studies will consider the structure relationships of these agents and, in particular, the relatively unstable nature of cefaclor. Mechanistic studies are planned concerning specific protein-drug interactions and levodopa absorption and also the influence of saturable first-pass metabolism in ethyl alcohol absorption, and interactions between this phenomenon and delayed alcohol absorption due to food.